Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

cGMP and opening of mitochondrial K(ATP) channel play an important role in preconditioning of the heart following ischemia/reperfusion (I/R) injury. We investigated the cardioprotective effect of vardenafil (VAR) (Levitra), a highly selective and biochemically potent inhibitor of phosphodiesterase-5 (PDE-5) that enhances erectile function in men through up-regulation of cGMP. Rabbits were treated with VAR (0.014 mg/kg, iv) or volume-matched saline, 30 min prior to 30 min of sustained regional ischemia followed by 3 h of reperfusion. 5-hydroxydecanoate (5-HD, 5 mg/kg, iv) or HMR 1098 (HMR, 3 mg/kg, iv), the respective blockers of mitochondrial or sarcolemmal K(ATP) channels were administered 10 min before I/R. Infarct size was measured by computer morphometry of tetrazolium stained sections. Vardenafil treatment caused decrease in mean arterial blood pressure from 93.5+/-2.6 to 82.2+/-1.5 mmHg and increase in heart rate from baseline value of 151+/-20 to 196+/-4.6 bpm (mean+/-standard error of mean (S.E.M.), P<0.05) within 5 min. The infarct size (% of risk area) was reduced from 33.8+/-1.3 in control rabbits to 14.3+/-2.2 (58% reduction, P<0.05). 5-HD abolished VAR-induced protection as demonstrated by increase in infarct size to 34.5+/-2.3 (P<0.05, N=6 per group). In contrast, HMR failed to block the protective effect of VAR (infarct size, 14.3+/-2.2 versus 16.3+/-1.0 in VAR + HMR, P>0.05). Neither inhibitors of the K(ATP) channel influenced the infarct size in the control rabbits, as shown by infarct size of 34.9+/-1.1 and 33.3+/-1.4 in animals treated with 5-HD and HMR, respectively. For the first time, we demonstrate that VAR induces protective effect against I/R injury via opening of mitochondrial K(ATP) channel. These results further support our hypothesis that the novel class of PDE-5 inhibitors induce protective effect in the ischemic heart, in addition to their well known clinical effects in the treatment of erectile dysfunction in men.
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PMID:Vardenafil: a novel type 5 phosphodiesterase inhibitor reduces myocardial infarct size following ischemia/reperfusion injury via opening of mitochondrial K(ATP) channels in rabbits. 1648 Jul 39

Phosphodiesterase-5 (PDE-5) inhibitors including sildenafil and vardenafil induce powerful preconditioning-like cardioprotective effect against ischemia/reperfusion injury through opening of mitochondrial K(ATP) channels in the heart. The goal of these studies was to demonstrate the protective effect of sildenafil and vardenafil on reperfusion injury and to compare it with the antianginal vasodilator nitroglycerin (NTG). In addition, we determined the role of mitochondrial K(ATP) channels in protection. Adult male New Zealand white rabbits were anesthetized and subjected to ischemia by 30 min of coronary artery occlusion followed by 3 h of reperfusion. Seven groups were studied. 1-Controls; 2-Sildenafil (total dose: 0.71 mg/kg; i.v.) infused for 65 min starting 5 min before reperfusion; 3-Sildenafil+5-hydroxydecanoate (5-HD, blocker of mitochondrial K(ATP) channel, total dose: 5 mg/kg) administered as 2 bolus injections; 4-Vardenafil (total dose: 0.014 mg/kg; iv) administered as in group 2; 5-Vardenafil+5-HD administered as in group 3; 6-5-HD administered as two bolus injections and 7-Nitroglycerin (NTG, total dose: 2 microg kg(-1) min(-1)) administered as in group 2. Infarct size was reduced in sildenafil (19.19+/-1.3%) as well as vardenafil (17.0+/-2.0%) treated groups as compared to controls (33.8+/-1.7%). However, NTG failed to confer similar cardioprotection (31.5+/-0.8%). 5-HD blocked the cardioprotective effects of sildenafil and vardenafil as shown by an increase in infarct size (34.0+/-1.1% and 28.3+/-1.9%, respectively). Both sildenafil and vardenafil protect the ischemic myocardium against reperfusion injury through a mechanism dependent on mitochondrial K(ATP) channel opening.
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PMID:Sildenafil and vardenafil but not nitroglycerin limit myocardial infarction through opening of mitochondrial K(ATP) channels when administered at reperfusion following ischemia in rabbits. 1715 8

We investigated the effect of intraperitoneal vardenafil (1 mg/kg) administration during an ischemic period in a rat model of testicular torsion/detorsion (T/D). Twenty-one adult Wistar rats were equally randomized into a control group, a T/D group and a vardenafil group. The control group was designed to collect basal values for biochemical and histopathological parameters. The T/D group underwent testicular torsion for 1 hour. The vardenafil group received vardenafil (1 mg/kg) intraperitoneally at 30 minutes after torsion. All rats were sacrificed 4 hours after reperfusion to evaluate the tissue levels of malondialdehyde and total antioxidant status. Germ cell apoptosis was evaluated using the apoptosis protease activating factor 1 antibody in all groups. The expressions of endothelial nitric oxide synthase (NOS) and inducible NOS were also assessed in both testes of all rats. The malondialdehyde levels in the T/D group were significantly higher than in the control and vardenafil groups. There were also significant decreases in total antioxidant status in the T/D group compared with the control and vardenafil groups. Vardenafil treatment significantly reduced apoptosis protease activating factor 1, endothelial NOS and inducible NOS levels in the vardenafil group compared with the T/D group. Administration of 1 mg/kg vardenafil during testicular torsion decreased ischemia/reperfusion cellular damage. Our results indicate that the reduction in oxidative stress by vardenafil may play a major role in its cytoprotective effects.
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PMID:Vardenafil reduces testicular damage following ischemia/reperfusion injury in rats. 1960 29